Genotype x environment interaction: an old problem in a new field.
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Two previous studies, Martin et al. (J. Exp. Psychol. Anim. Behav. Process. 23 (1997) 183) and Dudchenko et al. (J. Exp. Psychol. Anim. Behav. Process. 23 (1997) 194), report that, compared to non-disoriented controls, rats disoriented before testing were disrupted in their ability to learn the location of a goal on a dry radial-arm maze task, but that both groups learned at the same rate in the Morris water maze. However, the radial-arm maze task was much more difficult than the water maze. In the current set of experiments, we examined the performance of control and disoriented rats on more comparable dry land and water maze tasks. Compared to non-disoriented rats, rats that were disoriented before testing were significantly impaired in locating a goal in a circular dry arena, but not a water tank. The results constrain theoretical explanations for the differential effects of disorientation on different spatial tasks.
Although there is evidence to suggest that the retrosplenial cortex is involved in spatial learning and memory, many lesion studies have left the more caudal part of this region intact so leaving its role untested. In the first experiment, rats with neurotoxic lesions of the caudal half of the retrosplenial cortex (RspC1) were tested on a reference memory task in the water-maze. The RspC1 animals were impaired on initial acquisition although they performed normally on a subsequent probe test. The second experiment looked at working memory in the radial-arm maze and water-maze. Animals with caudal retrosplenial lesions (RspC2) were unimpaired on the acquisition stage of the radial-arm maze task but were impaired when the task involved maze rotation to control for the possible use of intramaze cues. The RspC2 animals also took longer to learn the platform position on a delayed matching-to-place task in the water-maze. These results show a subtle impairment in spatial memory performance that is not as severe as that seen when more complete lesions of the retrosplenial cortex are made.
While hippocampal lesions impair learning and memory in many tasks, such lesions also enhance learning and memory in other tasks. The present experiment examines the effects of inactivation of the hippocampus with lidocaine prior to learning, to find food in a place or response version of a four-arm plus-shaped maze. Rats received lidocaine injections 6 min prior to training. Rats were trained in a single session to a criterion of 9/10 correct responses. Compared to artificial cerebrospinal fluid (aCSF)-injected controls, rats with intra-hippocampal injections of lidocaine exhibited significantly retarded acquisition of place learning. In marked contrast, rats with intra-hippocampal injections of lidocaine exhibited significantly enhanced acquisition of response learning compared to their controls. In addition to showing that the hippocampus is important for learning the place task, these findings suggest that processing of information by the hippocampus interferes with learning a task dependent on a different neural system.
Previous experiments have shown that infusions of ibotenic acid in the nucleus basalis magnocellularis (NBM) induce a strong impairment in spatial navigation for a hidden platform in the Morris water maze. This effect was initially attributed to a cholinergic deficit, but later studies showed that performance level did not correlate with the degree of cholinergic denervation. Therefore, this impairment is due to a combined cholinergic and non-cholinergic deficit. However, it is not clear in which particular processes the NBM is involved. In this study we have evaluated the origin of behavioural impairment in spatial navigation in the water maze after an ibotenic acid-induced lesion of NBM. In the first experiment, Wistar rats were trained preoperatively in an allocentric navigation task. Postoperatively, they were tested in the same task. All lesioned animals showed a performance level similar to controls. Lesions did not impede the acquisition of new positions in the water maze, nor did affect the ability of animals to remember new platform positions after an intertrial interval of 20s, even if animals had received only allocentric experience with the platform position, or allocentric and path integration information concurrently. Lesions also failed to affect the ability to locate a hidden platform in a new environment. However, hippocampal infusions of scopolamine (5 microg) produced a severe impairment in NBM-damaged animals, without impairing performance of controls. In the second experiment Wistar rats with the same lesion were first trained in a visual-guided task in the water maze, and subsequently evaluated in the spatial task. In both tasks lesioned animals were not different from controls. These results suggest that the NBM played an important role during acquisition phases but not in the execution of spatial navigation. Moreover, the excessive emotional response displayed by lesioned animals is postulated as a relevant cause for the impairment observed in spatial navigation after NBM damage.
Early detection of progressive diseases such as Alzheimer's Disease (AD) is crucial for both the treatment and study of the disease. Performance on a visuo-spatial paired-associates learning (vsPAL) task was recently shown to reliably predict a diagnosis of AD in aged populations. The present study reports the development of this vsPAL task for use in nonhuman primates. Translation of vsPAL to a nonhuman model may provide improved preclinical tools for study of the etiology and treatment of dementia. Twelve young adult male rhesus monkeys were trained to perform the vsPAL task concurrently with tests comprising a nonhuman primate neuropsychological test battery. Monkeys successfully learned to perform vsPAL and did so in a task-difficulty ranked fashion. Despite significant individual differences in capability in the acquisition of the recognition memory aspects of the task, all monkeys evidenced the ability to learn within-trial, i.e. to improve with repeated stimulus-location pairings. These results support the use of vsPAL performance under various challenge conditions to investigate the possible substrates of early cognitive decline in AD. Comparison of performance on vsPAL with performance on other memory tasks in the battery will be of more general use in differentiating mechanisms involved in various aspects of mnemonic function.
Spatial learning and memory in young and old dogs was studied in a series of experiments using a delayed non-matching to position (DNMP) paradigm. Past research from our laboratory has suggested that aged dogs perform more poorly on a version of the DNMP task compared to young dogs [Head et al., Spatial learning and memory as a function of age in the dog, Behav. Neurosci. 1995;109(5):851-585]. We have now extended these findings by testing a large number of dogs on three different variations of the DNMP paradigm to evaluate different aspects of spatial learning and memory. Our results indicate that: (1) aged dogs show impaired spatial learning compared to young dogs, (2) aged dogs display spatial working memory deficits compared to young dogs, (3) young dogs have a greater maximum working spatial memory capacity than old dogs and (4) we can use the DNMP paradigm to cognitively categorize different subsets of aged dogs. These data indicate that the DNMP paradigm can serve as a valuable tool to evaluate age-dependent cognitive dysfunction in the canine.
Recently, a receptor for the angiotensin II(3-8) (Ang IV) hexapeptide, was discovered in the hippocampus, suggesting a possible role in learning. The present study utilized intracerebroventricularly (icv) infused scopolamine hydrobromide (scop) to disrupt spatial learning in the circular water maze, followed by the Ang IV analog norleucine1-Ang IV (Nle1-Ang IV), to restore normal performance. Rats were icv pretreated with either scop or artificial cerebrospinal fluid (aCSF) followed by either icv injected Nle1-Ang IV or aCSF, and then behaviourally tested. During acquisition training, each animal's latency to locate the platform, path distance, speed, and efficiency ratios were measured. A probe trial was conducted on the final day of training and the time spent in the target quadrant and the number of crossings over the former location of the platform (annulus crossings) were observed. The results indicate that those animals treated with scop followed by aCSF performed poorly during acquisition training as compared with controls. In contrast, those animals that received scop followed by Nle1-Ang IV attained equivalent latencies, distances, and efficiency ratios to find the platform as those achieved by controls. There were no observed differences in swimming speed, thus arguing against drug-induced motor impairment. During the probe trial, animals treated with scop followed by aCSF spent less time in the target quadrant and made fewer annulus crossings as compared to controls, while the scop, Nle'-Ang IV treated animals performed equivalently to controls. These results suggest that Nle1-Ang IV acts to counteract the disruption of spatial learning induced by scopolamine.
The value of the results of the inverse dynamic analysis procedures used in the study of human tasks is dependent on the quality of the kinematic and kinetic data supplied to the biomechanical model that supports it. The kinematic data, containing the position, velocity and acceleration of all anatomical segments of the biomechanical model, result from the reconstruction of human spatial motion by means of the evaluation of the anatomic points positions that enable to uniquely define the position of all anatomical segments. Furthermore, the motion data must be kinematically consistent with the structure of the biomechanical model used in the analysis. The traditional photogrammetric methodologies used for the spatial reconstruction of the human motion require images of two or more calibrated and synchronized cameras. This is due to the fact that the projection of each anatomical point is described by two linear equations relating its three spatial coordinates with the two coordinates of the projected point. The need for the image of another camera arises from the fact that a third equation is necessary to find the original spatial position of the anatomical point. The methodology proposed here substitutes the projection equations of the second camera with the kinematic constraint equations associated with a biomechanical model in the motion reconstruction process. In the formulation the system of equations arising from the point projections and biomechanical model kinematic constraints, representing the constant length of the anatomical segments, are solved simultaneously. Because the system of equations has multiple solutions for each image, a strategy based on the minimization of a cost function associated to the smoothness of the reconstructed motion is devised. It is shown how the process is implemented computationally avoiding any operator intervention during the motion reconstruction for a given time period. This leads to an automated computer procedure that ensures the uniqueness of the reconstructed motion. The result of the reconstruction process is a set of data that is kinematically consistent with the biomechanical model used. Through applications of the proposed methodology to several sports exercises its benefits and shortcomings are discussed.
In sport science, as in clinical gait analysis, optoelectronic motion capture systems based on passive markers are widely used to recover human movement. By processing the corresponding image points, as recorded by multiple cameras, the human kinematics is resolved through multistage processing involving spatial reconstruction, trajectory tracking, joint angle determination, and derivative computation. Key problems with this approach are that marker data can be indistinct, occluded or missing from certain cameras, that phantom markers may be present, and that both 3D reconstruction and tracking may fail. In this paper, we present a novel technique, based on state space filters, that directly estimates the kinematical variables of a virtual mannequin (biomechanical model) from 2D measurements, that is, without requiring 3D reconstruction and tracking. Using Kalman filters, the configuration of the model in terms of joint angles, first and second order derivatives is automatically updated in order to minimize the distances, as measured on TV-cameras, between the 2D measured markers placed on the subject and the corresponding back-projected virtual markers located on the model. The Jacobian and Hessian matrices of the nonlinear observation function are computed through a multidimensional extension of Stirling's interpolation formula. Extensive experiments on simulated and real data confirmed the reliability of the developed system that is robust against false matching and severe marker occlusions. In addition, we show how the proposed technique can be extended to account for skin artifacts and model inaccuracy.
In an immersive visualization experiment, participants performed a conjunction search task while standing either in open (heels 10 cm apart, feet at a comfortable angle) or closed stance (feet pressed together). In the world-frame condition, the search display maintained its position in space as the participant swayed, generating optic flow informative about sway. In the head-frame condition, the display maintained constant distance and orientation with respect to the participant's head, providing no visual information about sway. In both conditions, participants (surprisingly) searched faster while in the more difficult closed stance. Interpretation of this result is unclear. Participants also swayed more as search-load increased, and made more errors in the high search-load condition. It is suggested that this performance tradeoff is a result of the sharing of a limited-capacity, modality-non-specific spatial-attentional resource between postural and suprapostural tasks.
The ventrolateral-ventromedial (VL-VM) nuclei are classified as a motor area of the thalamus on the basis of predominant input from the cerebellum and the basal ganglia and output to the motor cortex. The sensitivity to electrolytic lesions of the VL-VM thalamic nuclei in rats was evaluated for tests requiring balance and equilibrium. VL-VM lesions impaired acquisition of the rotorod test but had no effect on stationary beam and hole-board tests. A selective impairment was also observed in the Morris water maze, as VL-VM thalamic lesions slowed down acquisition of the hidden platform but not the visible platform condition. These results support the hypothesis that thalamic motor nuclei participate in the acquisition of sensorimotor and spatial learning.
The recently discovered peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOR share many structural similarities with the opioid peptides and their receptors. The anatomical distributions of N/OFQ and NOR are similar to those of opioid peptides and receptors. In addition, NOR and opiate receptors couple via the same G-proteins to similar effectors, such as Ca(2+) channels, K(+) channels, adenylyl cyclase, and several protein kinases. Thus, the behavioral effects of N/OFQ have been investigated in the context of known opiate effects, and a possible connection has been sought between the effects of these two homologous signaling systems. Originally characterized as a nociception-producing peptide, N/OFQ has now been shown to have diverse effects on nociception, as well as effects on many other behaviors. With regard to nociception, the peptide has been reported to produce hyperalgesia, reversal of opioid-mediated analgesia, analgesia, and allodynia. N/OFQ also has effects on other behaviors, such as locomotion, feeding, anxiety, spatial attention, reproductive behaviors, and opiate tolerance. The relationship between opiates and N/OFQ is strengthened by the fact that opiates also affect these behaviors. However, the exact nature of the relationship of N/OFQ with opiates-opiate-like versus antiopiate-remains controversial. This review will detail the diverse effects of N/OFQ and suggest that this peptide, like other putative antiopiate peptides, can be described as 'opiate modulating. '
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Aged rats show decrements in performance on cognitive tasks that require the use of spatial learning and memory. We used the 8-arm radial water maze (RAWM) to measure spatial learning as a function of age in young (6 months) and old (21 months) male F344 rats. Rats were placed in the RAWM in different start arms with the same goal arm for 3 days (five trials/day); the goal arm was changed on day 4. Old rats demonstrated spatial impairment as evidenced by increased latencies to find the hidden platform on day 4. Old rats made significantly more errors, both reference and working memory errors, than young rats on all days. It is likely that the old rats utilized non-spatial strategies to solve the task, and therefore were impaired in learning a new platform location. The RAWM is a reliable, sensitive, and powerful additional test to assess age-related spatial learning and memory deficits, combining the advantages of the Morris water maze and the radial arm maze while minimizing the disadvantages.
Spatial learning tasks are sensitive to functional decline in aged laboratory rodents. This is a review of recent work that has examined both the nature of age-related impairments on spatial tasks, and the relation of such deficits to underlying neurobiological mechanisms. The review supports the notion that hippocampal dysfunction underlies the mild/moderate cognitive decline that often accompanies normal aging. Thus the spatial learning deficit in aged rodents is a promising model for understanding the effect of age on brain systems that serve a memory function in humans.
Research with laboratory rats and humans demonstrating that the usual age-related deficits in spatial working memory can be attenuated or eliminated by prior training earlier in adult life is reviewed and possible mechanisms for this phenomenon are considered. A new technique for measuring remote memory for spatial information in humans is described and preliminary results with demented patients are discussed.
Evidence for age-related changes in spatial memory in rodents and humans is presented, along with data that suggest that the hippocampal formation is necessary for normal performance on spatial tasks in both species. An examination of the electrophysiological characteristics of this structure in rats suggests that the changes that occur with age in the hippocampus are selective, but that at least two primary types of alterations contribute to the spatial cognitive impairment seen in these animals. These include a deficit in the ability to maintain synaptic enhancement and a reduction in the accuracy of information processing ability of single hippocampal neurons.
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